Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2018; 64(3): 9-17


INFLUENCE OF OPENER OF KATPCHANNELS OF FLOCALIN ON OXIDATIVE METABOLISM, THE ACTIVITY OF NOSYNTHASES AND BLOOD OXYGENATION

R.B. Strutynskyi, Yu.P. Korkach, V.R. Strutynskyi, R.A. Rovenets

    O.O. Bogomoletz Institute of Physiology National Academy of Science of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz64.03.009


Abstract

In the experiments on the anesthetized dogs, the effects of ATP-sensitive potassium (KATP) channels activation by flocalin on the activity of endothelial and inducible NO-synthases (iNOS), heme oxygenase reaction, blood oxygenation and free radical processes were studied. Changes in biochemical parameters in arterial blood were determined after 20 and 60 minutes after intravenous administration of flocalin in doses of 0.1, 0.5, 1.0 and 1.5 mg/kg. It is shown that the opening of KATP-channels dose-dependent increases the level of protective constitutive synthesis of nitric oxide and, conversely, inhibits inducible synthesis (at 2.8 and 2.1 times at a dose of flocalin 1.5 mg/kg, respectively). The activation of the above channels is a powerful antihypoxic mechanism – greatly enhances the oxygenation of arterial blood and the content of nitrite anion (at 3.7 and 3.0 times at a dose of 1,0 mg/kg, respectively). Flocalin significantly reduced the content of the products of the heme oxygenase reaction - iron and bilirubin (with a maximum effect of 2.9 and 1.9 times respectively), which may indicate inhibition of the activity of the enzyme heme oxygenase. Аctivation of KATP-channels dose-dependently suppresses free radical processes (decrease in the generation of superoxide anion and hydrogen peroxide (5.3 and 7.2 times at a dose of 1.5 mg/kg, respectively) and exhibits antioxidant properties (decrease in the content of diene conjugates by 6.3 times at a dose of 1.5 mg/kg), inhibits the formation of peroxynitrite by reducing the generation of superoxide anion (uric acid content) and inducible nitric oxide. Thus, the activation of KATP-channels by flocalin increases the constitutive synthesis of NO and, conversely, reduces the inducible synthesis of NO, greatly enhances the oxygenation of arterial blood, suppresses free radical processes and the activity of heme oxygenase.

Keywords: ATP-sensitive potassium channels; flocalin; NOsynthases; free radicals; heme oxygenase

References

    Nichols CG. KATP channels as molecular sensors of cellular metabolism. Nature. 2006 Mar 23;440(7083):470-6. doi: 10.1038/nature04711. CrossRef   Olson TM, Terzic A. Human KATP channelopathies: diseases of metabolic homeostasis. Pflugers Arch. 2010 Jul;460(2):295-306. doi: 10.1007/s00424-009-0771-y. CrossRef   Zingman LV, Hodgson DM, Alekseev AE, Terzic A. Stress without distress: homeostatic role for KATP channels. Mol Psychiatry. 2003 Mar;8(3):253-4 doi:10.1038/ sj.mp.4001323.   Alekseev AE, Hodgson DM, Karger AB, Park S, Zingman LV, Terzic A. ATP-sensitive K+ channel channel/enzyme multimer: Metabolic gating in the hearts. J Mol Cell Cardiol. 2005 Jun;38(6):895-905. doi:10.1016/j. yjmcc.2005.02.022.   Zhou M, He HJ, Tanaka O, Sekiguchi M, Kawahara K, Abe H. Different localization of ATP sensitive K+ channel subunits in rat testis. Anat Rec (Hoboken). 2011 Apr;294(4):729-37. doi: 10.1002/ar.21348. CrossRef   Strutyns'kyi RB, Rovenets' RA, Neshcheret OP, Tumanovs'ka LV, Boichuk TM, Dzhuran BV, Moibenko OO. Effect of medical form of flocalin on the course of myocardial reperfusion injury. Fiziol Zh. 2011;57(1):55-65. PubMed   Alekseev AE, Reyes S, Yamada S, Hodgson-Zingman DM, Sattiraju S, Zhu Z, Sierra A, Gerbin M, Coetzee WA, Goldhamer DJ, Terzic A, Zingman LV. Sarcolemmal ATP-sensitive K+ channels control energy expenditure determining body weight. Cell Metab. 2010 Jan;11(1):58- CrossRef PubMed PubMedCentral   doi: 10.1016/j.cmet.2009.11.009. CrossRef   Strutyns'kyi RB. The vasodilation effects of flokalin, a fluorine-containing K (ATP) channel opener. Fiziol Zh. 2010;56(4):59-65. PubMed   Voitychuk OI, Strutynskyi RB, Yagupolskii LM, Tinker A, Moibenko OO, Shuba YM. Sarcolemmal cardiac KATP channels as a target for the cardioprotective effects of the fluorine-containing pinacidil analogue, flocalin. Br J Pharmacol. 2011 Feb;162(3):701-11. doi: 10.1111/j.1476- 5381.2010.01072.x.   Strutyns'kyi RB, Rovenets' RA, Strutyns'ka NA, Neshcheret OP, Moibenko OO. The influence of activation of the ATP-sensitive potassium channels by flocalin on the function of the cardiovascular system. Fiziol Zh. 2013;59(1):11-6. PubMed   Strutynsk'kyiR B, Moibenko OO. Modeling of K+ATP channel activity in normotensive and hypertensive animals. Fiziol Zh. 2000;46(6):54-60. PubMed   Burbello AT, Shabrov AB, Denisenko PP. Modern medicines. Clinico-pharmacological guide for a practitioner. Sankt Petersburg, Moscow: Neva, 2006.   Jahandir A, Terzic A. KATP channel therapeutics at the bedsise. J Mol Cell Cardiology. 2005, 39: 99–112. CrossRef PubMed PubMedCentral   Pyvovar SM, Strutyns'kyi RB, Iagupol's'kyi LM, Moibenko OO. Study of the mechanism of action of novel fluoro-containing analogs of diazoxide on the vascular tonus. Fiziol Zh. 2004;50(2):27-33. [Ukrainian]. PubMed   Strutyns'kyi RB, Kotsiuruba AV, Neshcheret OP, Rovenets' RA, Moibenko OO. The changes of metabolism in myocardium at ischemia-reperfusion and activating of the ATP-sensitive potassium channels. Fiziol Zh. 2012;58(1):13-26. [Ukrainian]. PubMed   Salter M, Knowles RG, Moncada S. Widespread tissue distribution, species and changes in activity of Ca2+- dependent and Ca2+-independent nitric oxide syntases. FEBS Lett. 1991, 291(1):145-49. CrossRef   Boyde JR, Rahmotullah M. Optimization of conditions for the colorimetric determination of citrulline, using diacetil monoxime. Anal Biochem. 1980,107:424-31. CrossRef   Gerdel D, Cederbaum AJ. Inhibition of the catalitic activity of alkoholdegydrogenase by NO is associated with S-nitrosylation and the release of zinc. Biochemistry. 1996,35(50):16186-94. CrossRef PubMed   Strutyns'kyi RB, Kotsiuruba AV, Neshcheret OP, Shysh AM, Rovenets' RA, Moibenko OO. Cardioprotective effects of activation of ATP-sensitive potassium channels in experiments in vivo: influence on blood biochemical parameters following ischemia-reperfusion of the myocardium. Fiziol Zh. 2009;55(6):12-9. PubMed   Lapkin VZ, Tikhadze AK, Belenkov Yu.N. Free radical processes in normal and pathological conditions. M., 2001.   Mkhitaryan LS, Kuchmenko OB. Oxidative stress: mechanisms of development and role in pathology. Kiev, 2004.   Moibenko OO, Sahach VF, Tkachenko MM, Korkushko OV, Bezrukov VV, Kul'chyts'kyi OK, Stefanov OV, Soloviov AI, Mala LT, Frol'kis VV. Mechanisms of nitric oxide activity in cardiovascular system as a basis of pathogenetic therapy of related diseases. Fiziol Zh. 2004;50(1):11-30.   Dudzinski DM, Igarashi J, Greif D, Michel T. The regulation and pharmacology of endothelial nitric oxide synthase. Annu Rev Pharmacol Toxicol. 2006;46:235-76. CrossRef PubMed   Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med. 2003 Dec;9(12):1498-505. CrossRef PubMed   Zweier JL, Samouilov A, Kuppusamy P.Non-enzymatic nitric oxide synthesis in biological systems. Biochim Biophys Acta. 1999 May 5;1411(2-3):250-62. CrossRef   Riondel J, Glise D, Fernandez-Carlos T, Favier A. In vitro comparative study of cytolysis mediated by natural killer cells towards malignant cells preincubated with antioxidants. Anticancer Res. 1998 May-Jun;18(3A): 1757-63. PubMed   Voitychuk OI, Strutynskyi RB, Moibenko OO, Shuba YM.Effects of fluorine-containing opener of ATPsensitive potassium channels, pinacidil-derivative flocalin, on cardiac voltage-gated sodium and calcium channels. Naunyn Schmiedebergs Arch Pharmacol. 2012 Nov;385(11):1095-102. doi: 10.1007/s00210-012- 0792-5.  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.